Upregulation of TRPM8 can promote the colon cancer liver metastasis through mediating Akt/GSK-3 signal pathway.

Abstract

This study aims to clarify the function of transient receptor potential melastatin 8 (TRPM8) in colon cancer liver metastasis. First, TRPM8 expression was determined by Western blotting in colon cancer patients with/without liver metastasis. Second, colon cancer cells were grouped into Mock, siCON, and siTRPM8 groups. Then, a series of in vitro experiments were conducted. Last, CT26 cells were used to construct colon cancer liver metastasis models on mice in vivo, followed by comparison of liver metastasis and determination of AKT/glycogen synthase kinase-3β (GSK-3β) pathway. Consequently, TRPM8 was upregulated in both colon cancer patients with/without liver metastasis, especially in those with metastasis. Compared with Mock and siCON groups, cells in siTRPM8 group demonstrated significant decreases in clone numbers, cell invasion, and migration; and obvious downregulations of p-AKT/AKT, p-GSK3β/GSK3β, Snail, and Vimentin, with an upregulation of E-cadherin. For in vivo experiments, a sharp decrease was observed in metastatic liver of mice in siTRPM8 group, with significant downregulations of p-AKT/AKT, p-GSK3β/GSK3β, Snail, and Vimentin and an upregulation of E-cadherin, as compared with Mock and siCON groups. Thus, TRPM8 was upregulated in colon cancer patients with liver metastasis, and silencing TRPM8 may suppress the progression and epithelial-mesenchymal transition of colon cancer cells to block its liver metastasis possibly by inhibiting AKT/GSK-3β pathway.